A hypothesis has been proposed to explain the mechanism of neutralization and the basis for the one-hit kinetics of the reaction, based on studies with polioviruses. The generality will be tested by examining the interaction of antibody with other viruses - similar (e.g., picornaviruses) and dissimilar (e.g., other icosahedral, enveloped, bacterial viruses). Studies have been initiated to understand the basis for the conformational instability observed with polioviruses. The unique manner of protein synthesis, and the manner of maturation of the protein coat of the picornaviruses is presently considered a possible clue to this phenomenon. Previous studies on uncoating of poliovirus have indicated that it is a multi-stage reaction. An in vitro system has been developed capable of carrying out the first stage. The active factor is present in a subcellular fraction rich in plasma membrane, and is probably a lipoprotein of high molecular weight. It reacts with viruses by a non-enzymatic mechanism. First stage uncoating is represented by a modification induced in the viral protein that renders it sensitive to proteolytic enzymes and detergents. Viral RNA is, however, not sensitive to RNase but can be made so by treatment of the modified particle with protease or dertergent. Studies will be continued to determine the nature of the induced change, and attempts will be made to isolated the cellular factor responsible for the second stage, i.e., release of the genome.